Fred E. Williams

The effects of liver denervation on food and water intake in the rat

Abstract In Experiment 1, liver denervations or sham operations were performed on rats in two separate trials. Food and water intakes and body weights of denervated rats did not deviate significantly from their sham operated controls. Male and female rats responded similarly. In Experiment 2, in addition to daily food and water intakes, initial daily meal size was investigated in two groups of liver denervated and sham operated rats. Initial daily meal size was determined during a one hour test at the start of the dark period of the light:dark cycle. In one group of rats a chow diet was used for testing, while a liquid diet was utilized in the second group. According to the “liver glucoreceptor preabsorptive satiety and general food intake control hypothesis” the denervated rats should have experienced a depression of daily food intake and preabsorptive satiety. No differences were found in either preabsorptive satiety or daily food and water intakes and body weights when denervated rats were compared to sham operated control animals. The results question whether liver glucoreceptors have any detectable influence on the control of feeding behavior. Certainly the data does not support the role of liver glucoreceptors as a major controller of feeding behavior in the rat.

The effect of liver denervation on meal patterns, body weight and body composition of rats

Neural liver glucoreceptors have been proposed as a primary controller of food intake (FI). Male Sprague-Dawley rats were either sham operated or liver denervated (LD). LD rats had all tissue cut between the liver and the esophagus, stomach and upper 1 cm of the duodenum. The hepatic artery and surrounding tissue were also removed. Finally the hepatic portal vein and the bile duct were stripped clean and the former phenol treated. Three days after surgery animals were placed in modules for continuous computer monitoring of feeding behavior. At no time after surgery did the daily food intake or body weight of the groups differ significantly. Meal size and frequency (light-dark distribution) were determined for 6 days and averaged. Neither parameter was altered by LD. During the next 6 months food intake and body weights of the groups did not differ significantly. At sacrifice, body composition was directly determined with no significant differences observed between LD and sham operated rats. LD were confirmed histologically. Monoamine histofluorescence of the livers of rats subjected to liver denervation revealed an absence of the normal fluorescence seen on small blood vessels in liver parenchyma of sham operated rats. The data do not support the concept that liver glucoreceptors are a major controller of FI.

Influence of three membrane types on healing of bone defects

OBJECTIVES To determine and compare osseous regeneration associated with three guided tissue regeneration membrane types (expanded polytetrafluoroethylene, dense polytetrafluoroethylene, and an absorbable polylactic acid/citric acid ester base) and removal forces required for expanded and dense polytetrafluoroethylene membranes. STUDY DESIGN Bilateral osseous defects were created in 30 adult rat calvaria; one defect was covered with a test membrane and the other received no membrane (control). After 2 or 4 weeks, forces required for membrane removal from the tissues were electronically determined, and the calvaria removed and decalcified. Sections through the defects were stained and evaluated electronically and microscopically. Data were analyzed statistically. RESULTS Microscopic evaluation with Mann-Whitney U test revealed that dense polytetrafluoroethylene was associated with significantly greater bone formation than expanded polytetrafluoroethylene (p = 0.02) at 2 weeks and absorbable polylactic acid/citric acid ester base (p = 0.004) at 4 weeks. Electronic evaluation of the linear degree of fill with one way ANOVA and Tukeys test found no significant difference (p > 0.05) among the experimental or the control groups. In addition, the Mann-Whitney U test indicated that removal forces required for dense polytetrafluoroethylene were significantly less than for expanded polytetrafluoroethylene (p = 0.003). CONCLUSIONS The use of dense polytetrafluoroethylene as a membrane barrier deserves further investigation as it allows osseous regeneration, it is easier to remove from healing soft tissues, and it is inexpensive. A study with larger sample sizes should be conducted.

Liver denervation attenuates the hypophagia produced by an imbalanced amino acid diet.

We observed previously that totally liver denervated (TLD) rats consumed more of an imbalanced amino acid diet (IAAD) than sham-operated controls (CON). For the present study rats were either CON, TLD, had only the hepatic-vagal branch cut (HVX), or had all nerves on the hepatic artery and portal vein removed (HAPV) (n = 10-11). The rats were prefed a purified basal diet for 9 days then switched to an isoleucine IAAD for 7 days. On days 2-5 all experimental groups consumed more (p < 0.05) of the IAAD than the CON; they also showed less (p < 0.01) weight loss on days 3-7. This experiment showed that either total or partial liver denervations enhanced the intake of an IAAD compared to CON. However, when one considers the anatomical arrangement of the nerves and the surgery technique employed the vital neural pathway may involve the hepatic vagal branch.

The effect of portal and jugular infused glucose, mannitol and saline on food intake in dogs.

Hepatic glucoreceptors have been hypothesized to have an important role in determining normal hunger and satiety. In the present study 23 dogs were fitted with chronic hepatic portal and jugular vein cannulas. The dogs were fed for 1 hr/day. On infusion days (total of 318 infusions) the animals were infused into the portal or jugular veins with a 30% glucose solution (2.4 or 3.6 g/kg, b.wt.), 0.9% NaCl as a volume control or 30% mannitol as an osmotic control and then fed 10 minutes later. The data showed that the dogs food consumption was similar after they received glucose or the appropriate control infusion regardless of the infusion site. Some dogs had blood samples taken for glucose and insulin determinations prior to infusion, at the middle and end of infusion, just prior to food presentation and at the end of the feeding period. Saline and mannitol infusions did not alter plasma glucose or insulin concentrations; whereas there were marked increases in plasma glucose (6-8 x) and insulin (18-19 x) following glucose infusions. Postinfusion glucose values indicated approximately 72% of the infused dose glucose (approximately 43 g) had left the plasma prior to food presentation. Despite the large increases in plasma glucose and insulin, as well as glucose storage and/or oxidation, the dogs consumed amounts of food similar to that eaten after control infusions. Similarly, prefeeding the dogs 20% of their average daily intake prior to infusion did not alter the animals subsequent intake. These data are in agreement with earlier work from our laboratory and question the role of the hypothesized hepatic glucose satiety receptors.

Liver denervation, 5-HT3 receptor antagonist, and intake of imbalanced amino acid diet.

The serotonin3 receptor antagonist ICS 205-930 (ICS) may act peripherally to attenuate the anorectic response of rats given an imbalanced amino acid (IMB) diet. Rats were divided into four groups: SHAM+saline (sal); SHAM+ICS; total liver denervation (TLD) + sal; and TLD+ICS. Rats were then given a purified basal diet for 16 days. Next, the groups were injected with sal or 9 mg/kg BW of ICS at 0800 h and at 0900 h (lights out) an isoleucine IMB diet was presented. By 12 h postinjection, the food intake (FI) of TLD and SHAM rats receiving ICS was similarly higher (p < 0.02) than sal-injected counterparts whose FI was also similar; BW followed FI. By day 3, the SHAM groups had similar low FI, whereas the FI of the TLD groups was increasing. The above study was repeated with similar results. Liver innervation is not required for ICS attenuation of IMB diet-induced hypophagia. Also, while sal-injected TLD rats show a normal attenuation of consumption of the IMB diet on the first day of exposure, they subsequently consume more of the IMB diet than SHAM rats. The reason for this difference in TLD rats is not clear but may be related to metabolism of the IMB diet or possibly learning.

Autonomic efferents affect intake of imbalanced amino acid diets by rats

An anorectic response occurs following ingestion of imbalanced amino acid (IMB) diets. There are three phases to this response: 1, recognition of the IMB diet; 2, conditioned development of an aversion to the IMB diet; and 3, adaptation. Blockade of peripheral serotonin-3 (5-HT3) receptors or vagotomy attenuates Phase 2 of the anorectic response. We investigated whether sympathetic efferents interact with the ventral gastric branch (VGB), by cutting it (X), or with the 5-HT3 receptor in these responses. First, VGBX and sham-operated (SHAM) groups were injected with vehicle or phenoxybenzamine (alpha-blocker), or nadolol (beta-blocker) before introducing the IMB diet. At 3 h suppression of the IMB diet ingestion was unchanged, showing no sympathetic efferent effect on Phase 1. Intake of the IMB diet increased 12-24 h later only in the SHAM+phenoxybenzamine group, so the VGB was necessary for alpha-blockade to enhance IMB diet intake during Phase 2 or possibly Phase 3. On days 2-5, intakes by the SHAM+phenoxybenzamine, VGBX+phenoxybenzamine and VGBX+nadolol groups were elevated. Therefore, alpha-blockade enhanced adaptation alone, but VGBX was necessary for beta-receptor blockade to augment Phase 3 adaptation. Both sympathetic efferents and the VGB are involved in Phases 2-3. Second, rats received vehicle or nadolol or scopolamine (nonselective muscarinic blocker) or pirenzepine (muscarinic M-1 receptor blocker),w+/-tropisetron (5-HT3 blocker). Pirenzepine attenuated the tropisetron effect between 6-9 h, but then pirenzepine and nadolol enhanced the tropisetron effect between 9-12 h. Scopolamine attenuated the tropisetron effect between 9-12 h. While neither experiment showed effects during the recognition phase, the autonomic and serotonergic systems interact in the learned and adaptive responses to IMB diets.

Suppressive effects of naloxone on food and water intake in vagotomized rats

Rats were (1) sham operated and ad lib fed, (2) given bilateral subdiaphragmatic vagotomies or (3) sham operated and pair fed to the vagotomized group. At the start of the dark period, following a 24 hr fast, the animals were tested for the ability of naloxone (0.5, 1.5, 3.0 and 5.0 mg/kg body weight) to suppress food and water consumption. In comparison to saline control injections the data indicated that naloxone was equally effective in suppressing food intake, over a two hour period, in all groups. Similarly naloxone effectively decreased water consumption of all groups in comparison to their saline trials. When the post naloxone data were calculated as a percentage of saline baseline this suppression was, at times, slightly greater in the vagotomized group than in the other groups. However, this may be an artifact of the low baseline intake of the vagotomized group. The results are discussed with relevance to the recent findings of others concerning this subject.